b-Defensins are the most ancient family of vertebrate defensins compared with a- and t-defensins. b-Defensin-like sequences have been found in the rattlesnake, orange-spotted grouper, and zebrafish, suggesting that the primordial gene for ß-defensins appeared before the fish-primate split about 450 million years ago. In contrast, α-defensins were derived from b-defensins after divergence of glires and rodents from other mammals about 91 million years ago, whereas t-defensins did not appear until primates separated from other mammals around 23 million years ago. human b-defensin gene (DEFB133) has also been mapped to 6p12.3, and its orthologs have been found and localized in rodent and canine genomes DEFB133/Defb49 lineage, on the other hand, contains a mutation in either the fifth or sixth cysteine in the mouse and human but is fully conserved with six canonical cysteines in the rat.